The patient recovered a medical sample on a shipwreck while diving in Bermuda. She broke the jar and was exposed to what turned out to be scabs when she cut her hand on the glass.

The patient came to Princeton-Plainsboro Teaching Hospital and was assigned to their head of diagnostic medicine Dr. Gregory House. He told his team about her symptoms - fever, vomitting and bloodshot eyes. Dr. Taub thought it was just a bad case of the flu. Dr. House told them she may have been exposed to smallpox. Ms. Masters and Dr. Foreman reminded Dr. House that smallpox had been eradicated and didn’t exist outside of a laboratory. Dr. House told them that the patient had been exposed to scabs from a watertight jar. Dr. House had checked with the CDC which had confirmed smallpox might be able to survive in those conditions. Dr. House ordered them to isolate the patient, do blood draws for smallpox antibodies and vaccinations for the entire family. Dr. Foreman wanted to check for varicella and measles as well, and Dr. House agreed.

Julie was placed in isolation, and her mother, stepfather and stepbrother were isolated in a different room. Dr. Taub told the patient they suspected tetanus and Ms. Masters admitted that it might be smallpox even though it was very unlikely.

Dr. Taub thought the lab work contraindicated smallpox, but did point to another infection. The patient’s white blood cell count was very low. However, the tests for varicella and measles were also negative. Dr. House returned to smallpox. He noted that in divers, the pressure often drives material into the joints. Dr. Taub agreed the antibodies could be hiding there. Dr. House ordered a tap of her knee, elbow, shoulder and other joints.

Dr. Taub started the tap, but then found the skin pustules typical of smallpox behind her knee. He figured he had to call the CDC. They performed a full examination of her skin. They said they could use cidofovir, but it only works in 70% of cases. Ms. Masters was looking for dark purplish skin blotches that could indicate hemorrhagic smallpox, in which case her chances would be even worse. She did find a rash under Julie’s arm, which appeared to rule out smallpox.

The CDC arrived and ordered a lockdown. Dr. Dave Broda from the CDC arrived and told Dr. House’s team their isolation suits were inadequate. Dr. House informed Dr. Broda about the rash, but Dr. Broda said it didn’t rule out smallpox if it presented before the pustules. Dr. House insisted it presented after the pustules. Dr. Broda planned to airlift blood and tissue samples to Atlanta for DNA analysis, which would be ready in 18 hours. He ordered Dr. House out of the isolation room.

Dr. House’s team met back in his office. Ms. Masters noted that when they left, Julie was running a fever of 103F, but Dr. Taub told her to forget about the case. Ms. Masters wanted to continue the differential. Dr. Chase suggested molluscum contagiosum, but Dr. Foreman noted the only way to confirm was to compare lesions to differentiate, and they didn’t have access to the patient. However, Dr. House noted that they had received a copy of the captain’s log from the ship, which was preserved in a museum. Dr. House found a Dutch translator.

The translator found that only the African slaves on the ship had the same symptoms as Julie, and they had diarrhea as well. None of the European crew were sick. Dr. House noted that smallpox doesn’t have any racial disparity. Dr. Taub suggested sickle-cell anemia. However, Dr. Chase suggested it was more about class than race - Vitamin D deficiency making them more susceptible to malaria or Dengue fever. However, none of those cause pustules. Ms. Masters noted the crew would have had clean drinking water while the slaves would not - scrofula. They needed to test for tuberculosis, but the CDC would obviously not agree to it because if it was TB, it would be slow moving and not an urgent diagnosis. Dr. House suggested to Dr. Foreman that they tell Dr. Broda it was meningococcus, which acts faster. While they had access to test for it, they would in fact test for TB.

Dr. Foreman took the meningococcus diagnosis to Dr. Broda, but Dr. Broda was suspicious. The patient hadn’t had any seizures and he offered to do the test and Dr. Foreman still wanted to do the test himself. At that moment, Julie’s stepfather collapsed and complained of a headache. He also started bleeding. Dr. Broda thought this ruled out meningococcus and refused Dr. Foreman access.

The stepfather’s symptoms were also consistent with smallpox. However, Dr. House thought it was also consistent with tuberculosis, which can cause bleeding in the brain that could be mistaken for a headache. However, to confirm, they would need to do a CT Scan and it was unlikely that they would agree to move the stepfather to radiology. Dr. House’s strategy this time was to suggest a pneumoencephalograph. It wouldn’t require moving the patient, but it was an old and risky procedure and he felt Dr. Broda would agree to the CT Scan instead. Ms. Masters suggested just telling Dr. Broda the truth and reminded Dr. House his first gambit failed. Dr. House agreed to let her try, but told Dr. Chase to suggest the pneumoencephalograph when Ms. Masters failed.

Ms. Masters pointed out to Dr. Broda that either the CT Scan would rule out smallpox, or would allow Dr. Broda to be the first person to CT Scan a patient with smallpox. Dr. Broda agreed to give the stepfather a CT Scan. However, on the way to radiology, the stepfather developed pustules and was too dangerous to transport. He was returned to isolation.

Julie’s vital signs started to drop and she developed more pustules. The stepfather was getting worse faster. Dr. House figured there was nothing more to be done. However, Ms. Masters asked for a closer look at the rash under Julie’s arm. Dr. Broda said she could only do that through the glass - he wouldn’t allow her in the isolation room. Dr. Broda assured her the results would be back in eight hours and he would be happy to let her examine Julie if the test was negative.

Ms. Masters went to see the patient to see the rash. However, as Julie shifted, Ms. Masters noted that there were no lesions on the soles of Julie’s feet. She went to report to Dr. House that Julie didn’t have pustules on her palms or soles. However, the stepfather did have pustules on his palms and soles. Dr. House suddenly realized the stepfather got it from the vaccine - he’s immunocompromised. The stepfather had kidneycancer six years ago. Dr. Foreman said it was in remission, but if it had returned, it would explain why the vaccine would cause symptoms. He would improve on interferon if that were the case. However, it still didn’t explain Julie’s symptoms.

However, Dr. Broda was convinced both Julie and her stepfather had smallpox. Dr. Broda reminded Dr. House about how dangerous the virus is and that given his condition, he couldn’t open the door. Dr. House pointed out that the stepfather had blood in his urine, consistent with kidney cancer. However, Dr. Broda argued it was also consistent with late stage smallpox. Dr. House argued that if it were kidney failure from the virus, there would be waste mixed in making it brown, not red. Dr. Broda still refused to open the door. Dr. House went in anyway to administer the interferon without putting on an isolation suit.

Dr. Cuddy provided Dr. House with an isolation suit. The stepfather did not improve with the interferon. Dr. House called for his team. Dr. House put on the isolation suit, but had a limited oxygen supply.

The stepfather’s vital signs were getting worse and the pustules were still spreading. However, Julie still had no pustules on her soles. Dr. House wanted another diagnosis, but Dr. Foreman said the stepfather had the classic symptoms of smallpox. Dr. House was not developing symptoms, he advised the stepfather that he should probably say goodbye to his family and wheeled his bed closer to the isolation unit with his wife and son. After saying goodbye, his vital signs flatlined.

Dr. House’s air was running out and he realized that he would be exposed to the virus if he changed his canister.

Ms. Masters wanted to continue a differential, but Dr. Foreman pointed out it was almost certain the father had died of smallpox. Ms. Masters decided to go back to the translator and the ship log. She became intrigued about the ship’s cat. It obviously wasn’t a pet and was most likely kept on board to hunt mice and rats. She wondered if it got sick - smallpox wouldn’t affect a cat. The cat also would have kept mice and rats away from the crew, but not the slaves. The translator told them the cat died. Ms. Masters wondered if the cat lost its fur and the translator confirmed that it did. Mice don’t carry smallpox, but do carry rickettsialpox. She wanted to start Julie on doxycycline, but Dr. Broda refused because Julie was already on anti-virals. Ms. Masters wanted to examine the stepfather for eschars, small patches of dead black tissue which would confirm rickettsialpox. However, Dr. Broda refused and planned to bleach the body of the stepfather, which would prevent the spread of smallpox, but destroy any escars.

Ms. Masters went to Dr. House and convinced him to examine the body of the stepfather. He was reluctant, but agreed and finally removed his isolation gloves to make the examination easier once he realized it would also diagnose Julie. He finally found an escar on the stepfather’s left side. Julie was started on doxycyline. Dr. House removed his isolation suit. The results from Atlanta came back eliminating smallpox, and the hospital lockdown was lifted. Julie was allowed to see her mother and stepbrother.